Objetivo: O objetivo deste estudo foi avaliar se o uso de uma solução cristaloide balanceada induz menos alterações metabólicas do que o cloreto de sódio 0,9% em crianças submetidas à ressecção de tumor cerebral. Desenho: Estudo fase II, unicêntrico, de superioridade, randomizado e controlado, realizado no Instituto de Oncologia Pediátrica da Universidade Federal de São Paulo, Brasil. População: crianças com idade entre 6 meses e 12 anos submetidas à ressecção de tumor cerebral. Intervenção: O uso de uma solução cristaloide balanceada durante e após (por 24 horas) ressecção de tumor cerebral foi comparado ao uso de cloreto de sódio 0,9%. Eletrólitos séricos e gasometria arterial foram coletados em três momentos: antes da cirurgia (basal); após a cirurgia [pós-operatório imediato (POI)]; e no primeiro dia pós-operatório (1º DPO). Desfecho primário: O desfecho primário deste estudo foi a variação do cloro sérico (pós-préop Cl), definida como a diferença absoluta entre as concentrações plasmáticas medidas no POI e antes da cirurgia. Desfechos secundários: Como desfechos secundários, foram avaliadas as variações (pós-préop) dos outros eletrólitos e do excesso de bases (BE); a incidência de acidose hiperclorêmica; e o escore de relaxamento cerebral (ERC), avaliado pelo neurocirurgião por meio de escala de 4 pontos. Resultados: 53 pacientes foram incluídos no estudo e randomizados; 27 receberam solução balanceada (grupo SB) e 26, cloreto de sódio 0,9% (grupo NaCl 0,9%). O pós-préop Cl mediano foi significativamente menor no grupo SB [0 (-1,0; 3,0)] do que no grupo NaCl 0,9% [6 (3,5; 8,5)], p < 0,01. O pós-préop BE mediano foi menor [-0,4 (-2,7; 1,3) versus -4,4 (-5,0; -2,3), p < 0,01] e acidose hiperclorêmica menos frequente (4% versus 67%, p < 0,01) no grupo SB do que no grupo NaCl 0,9%. O ERC foi comparável entre os grupos. Conclusão: Em crianças submetidas à ressecção de tumor cerebral, o uso de solução cristaloide balanceada reduziu a variação do cloro sérico comparado ao uso de cloreto de sódio 0,9%. Esses achados respaldam o uso de soluções balanceadas em crianças submetidas à ressecção de tumor cerebral. Registro no Clinical Trials: NCT NCT02707549 / Objective: The aim of this study was to determine if the use of a balanced crystalloid induces less metabolic derangements than 0.9% saline solution in children undergoing brain tumor resection. Design: Phase II, single center, superiority, randomized and controlled trial performed at Instituto de Oncologia Pediátrica, Universidade Federal de São Paulo, São Paulo, Brazil. Population: Pediatric patients (age range, 6 months to 12 years) undergoing brain tumor resection. Intervention: Use of a balanced crystalloid solution during and after (for 24 h) brain tumor resection was compared to saline 0.9%. Serum electrolyte and arterial blood gas analyses were performed before surgery (baseline), after surgery, and at postoperative day 1. Primary outcome: The primary trial outcome was the preoperative to postoperative variation in serum chloride (post-preop Cl) measured as the absolute difference between \"after surgery\" and baseline plasma concentrations. Secondary outcomes: As secondary outcomes, we measured the post-preop of other electrolytes and base excess (BE); hyperchloremic acidosis incidence; and the brain relaxation score, a four-point scale evaluated by the surgeon for assessing brain edema. Results: Fifty-three patients were included in the study; twenty-seven were randomized to receive a balanced crystalloid (balanced group) and twenty-six were randomized to receive 0.9% saline solution (saline group). The median post-preop Cl (mmol l-1) was significantly lower in the balanced [0 (-1.0; 3.0)] than in the saline group [6 (3.5;8.5); p < .01]. Median post-preop BE (mmol l-1) was lower [-0.4 (-2.7; -1.3) versus -4.4 (- 5.0; -2.3); p < .01] and hyperchloremic acidosis less frequent (4% versus 67%; p < .01) in the balanced group than in the saline group. Brain relaxation score was comparable between groups. Conclusions: In children undergoing brain tumor resection, balanced crystalloid solution infusion reduced variation in serum chloride. These findings support the use of balanced crystalloid solutions in children undergoing brain tumor resection

As células-tronco adultas possuem capacidade de se transformar em certos tipos de tecidos. Surge desta forma, uma nova modalidade de tratamento para doenças cardíacas, assim, uma avaliação na distribuição e quantificação do número de células por diferentes vias de infusão tornam-se importantes, pois o microambiente e interação célula/célula interferem no processo de transdiferenciação e/ou fusão. Foram utilizados nove cães, com peso entre 25 e 30kg e hígidos, no qual foi realizada punção, separação, marcação e infusão de células mononucleares da medula óssea pelas vias intracoronariana, transendocárdica e venosa retrógrada. Pôde-se observar a presença de células por todo tecido cardíaco em todas as vias, contudo o padrão de distribuição das mesmas difere, no qual há um predomínio de células em tecido conjuntivo, principalmente em epicárdio nas vias transendocárdica e venosa retrógrada e um padrão intersticial muscular intracoronariana. Há diferenças significativas na quantidade de células nas regiões apical, basal, medial e apical quando relacionada à via de infusão (P&lt;0,01). / The adult stem cells have a capacity to transform in different kinds of tissue. It is emerges like a new treatment modality of cardiac diseases, so, an evaluation in cell distribution and quantification by different routes of infusion in heart are necessary, because the microenvironment and the interaction cell/cell age in the transdifferentiation and fusion process. It was used 09 healthy mongrel dogs, with 25 -30kg of weight, which was performed a punction of iliacal crest, bone marrow mononuclear cells separation by Ficoll density, stained with Hoechst and infusion by intracoronary, transendocardial and retrograde routes. The marked cells was observed in all cardiac tissue, however, the pattern of distribution of the same ones differs, however in the transendocardial and retrograde route the cells could be founded mainly into the connective tissue - epicardium and sub-epicardic connective tissue and in the intracoronary route, the cells was observed mainly in the muscular interstice. It was observed a significant number of cells in the atrial, basal, medium and apical cardiac region when related with the route of infusion.

The introduction of environmental education in schools has been the focus of a long campaign worldwide since the late 1960s. The difficulties in teaching environmental education, including the choice of curriculum models, and the obstacles to changing contemporary schooling patterns have been well documented. The traditional process of new subject emergence has been detailed in the literature; whether or not environmental education should or could follow this traditional pattern of subject emergence in schools is the focus of this thesis. In Taiwan, the introduction of environmental education in junior high schools occurred as part of a nationwide curriculum change in 2002. This research used an interpretive approach to explore the views and practices of staff in three typical Taiwanese junior high schools at this time. The focus of the research was to study what happened at the level of classroom teaching and school development. The research program was designed to interview both administrators and teachers before, during and after the first year (2002 school year) of curriculum implementation in each of the three case study schools. Three rounds of interviews were conducted over a period of three years (Sept. 2001 - June 2004). As well as interviews, national and school documents were collected; and announcements and decisions from the Ministry of Education and schools were documented. Also, because the reform encouraged the development of school-based curriculum, a questionnaire was given to the one school which chose environmental education as their school-based curriculum in order to better understand the emergence of environmental education in this school. The findings show a paradox in Taiwanese junior high schooling: although each school placed considerable value on environmental education, the data showed that the introduction of environmental education via an infusion strategy during a time of national curriculum change had minimal impact in the three Taiwanese case study schools. A cross-case analysis indicated the reason for this failure was the lack of effectiveness of eleven supporting themes often discussed in the emergence of a new subject: the possibility of gaining external examination credit and entry to a university department; the prioritising of the subject in school timetabling and programming; the development of a systematic syllabus; the presence of proactive support from central government leadership; the provision of teacher professional development; the inclusion in the informal as well as the formal curriculum in a school; the inclusion of environmental education in non-formal education in society; the presence of clear subject characteristics and definition; the presence of substantial school-based material interests; the gaining of support from an external constituency, especially parents; and the presence of an emergence process that couples internal value evolution with external compulsion. The Taiwanese case studies raised three particular and additional themes for the emergence of environmental education, specifically: the need to set up long-term partnerships with local groups that have an interest in or responsibility for the local environment (e.g. societies, agencies and non-governmental organisations) to achieve local environment involvement; the need for a whole school approach through curriculum integration to achieve the transformative nature of environmental education; and the need to build up a sound cooperative network that includes people at all levels of the education system and society to achieve a national cooperation network. These three particular themes derived from the nature of environmental education as a holistic, integrative and interdisciplinary subject. In summary, the findings not only confirmed the themes important for the emergence of environmental education and other contemporary school subjects, but they also raised particular themes pertinent to the emergence of environmental education. When these three particular themes are not taken into account, the effective emergence of environmental education in contemporary schooling, as exemplified by Taiwanese junior high schools, will be difficult to achieve in mainstream education.

Clinical diagnosis of vitamin B12/cobalt (Co) deficiency is difficult due to the unspecific nature of the clinical symptoms. The apparent increase in vitamin B12 deficiency in New Zealand in the late 1990’s made it clear that health providers were very reliant on plasma reference ranges to diagnose deficiency. However, the lack of quantitative data of what these reference ranges represent in terms of supply of vitamin B12, has prevented a better understanding of the metabolism of vitamin B12 within sheep. This thesis describes the development of an experimental approach to measure vitamin B12 production and absorption in sheep. The model was then used to investigate whether the type of carbohydrate source affects vitamin B12 production and/or absorption. In the first trial (Chapter 4), an adaptation of the repletion technique of Suttle (1974) for copper was used. Previously vitamin B12 depleted sheep were maintained on a diet of 400 g DM meadow hay and 250 g DM crushed barley and which provided a daily intake of 0.03 mg Co. Sheep were intravenously infused with known quantities of vitamin B12 (0 – 200 nmol hydroxycobalamin/d) to determine whether a relationship exists between plasma vitamin B12 concentration and rate of entry of the vitamin into the bloodstream and to quantify the relationship. Eight ewes fitted with rumen and abomasal cannulae were used in a paired 4x4 Latin square design. Four levels of vitamin B12 were infused into the jugular vein for 4 d followed by recovery period of 17 d and the plasma responses measured during this period. Control animals maintained relatively stable plasma levels while levels in treated animals rose sharply within 4 h after the start of infusion. The responses were proportional to infusion rate with a highly significant difference in concentrations observed between treatments (P<0.001). Appearance of vitamin B12 in the plasma was quantified by the relationship Y(pmol/l) = 238 + 102x0.74 where x = infusion rate(nmol B12/d), R² = 0.945. Plasma levels declined rapidly on cessation of infusion and had returned to original pre-treatment levels by the end of the recovery period. The second trial (Chapter 5) quantified plasma responses in relation to dietary Co supply to the rumen. The same eight rumen and abomasal cannulated ewes were used in a paired 4x4 Latin square with 4 levels of intra-ruminal Co infusion in amounts ranging from 0 – 1 mg Co/d as CoSO₄, infused for 4 d followed by a 19 d recovery period. Plasma vitamin B12 response was measured as were concentration of vitamin B12 in abomasal digesta supernatant and digesta liquid flow, the latter using polyethylene glycol as liquid phase marker. Plasma concentration increased from approximately 300 pmol/l to 750 – 800 pmol/l, peaking at day 5 after commencement of infusions. Control animals infused with water maintained base-line plasma vitamin B12 levels around 250 pmol/l. Digesta liquid flow was estimated at 14.6 l/d. The results from Chapters 4 and 5 allowed estimates of vitamin B12 production and absorption. These results are discussed and efficiency of capture of Co into vitamin B12 from dietary Co intake was estimated to decrease from 8.4% to 0.74% as Co intake increased from 0.03 to 1.11 mg Co/d. Absorption coefficient was estimated from the relationships between abomasal vitamin B12 flow and plasma response. The absorption coefficient was calculated to increase from 7 to 10% as abomasal vitamin B12 flow increased from 108 to 142 nmol/d. The current animal model was subsequently used in the final trial (Chapter 6) to investigate whether the type of carbohydrate supplied in the diet influences vitamin B12 production and absorption. The same eight ewes fitted with rumen and abomasal cannulae were used in a 2x4 cross-over design. Half of the ewes were maintained on the basal diet and crushed barley while, for the remainder, the barley was replaced by 250 g of fructose:sucrose in a 80:20 mix during a 7 d period of adaptation. While on their respective diets, both groups were then infused with 0.3 mg Co/d for 6 d, a level chosen to optimise plasma vitamin B12 response. All ewes were then returned to the basal diet and barley for a 15 d recovery period after which treatments were reversed and the procedure repeated. Rumen pH, valeric, propionic, butyric, succinic, and acetic acid and ammonia concentrations were not significantly affected by diet. Digesta flow was 30% greater on a diet enriched with starch compared to sugar-enriched diet. There was an observed difference in vitamin B12 production. However there was no significant diet x time effect on plasma vitamin B12 concentration so any difference in production was negated by a difference in absorption. Carbohydrate supplied as water soluble carbohydrate or starch does not appear to influence plasma vitamin B12 concentration.

Ce travail de recherche propose un modèle numérique pour simuler les procédés par infusion de résine en utilisant la méthode des éléments finis. Ce modèle permet de représenter l'écoulement d'une résine liquide dans des préformes poreuses subissant de grandes déformations. Dans cette étude, une modélisation macroscopique est utilisée. Au niveau du procédé, une zone de résine liquide est déposée sur les préformes. Ces dernières étant considérées comme un milieu poreux. Les équations de Stokes et de Darcy sont utilisées pour modéliser l'écoulement de la résine respectivement dans le drainant et dans les préformes. L'originalité du modèle réside dans le fait qu'un seul maillage est utilisé pour les deux milieux. La discrétisation est réalisée avec des éléments mixtes : dans Stokes, des éléments P1+/P1 sont utilisés et dans Darcy, des éléments P1/P1 stabilisés avec une formulation multi-échelle sont employés. Des fonctions distances signées sont utilisées pour représenter l'interface entre Stokes-Darcy et pour représenter le front de résine. Concernant la déformation des préformes, une formulation Lagrangienne réactualisée est utilisée. Dans cette formulation Lagrangienne, le comportement des préformes humides est représenté à l'aide du modèle de Terzaghi dans lequel les préformes sèches ont un comportement élastique non-linéaire. La perméabilité est reliée à la porosité via la relation de Carman-Kozeny. Celle-ci est déterminée à partir de l'équation de conservation de la masse. Ce modèle a été implémenté dans ZéBuLoN. Plusieurs simulations numériques d'infusion de résine sont présentées à la fin de ce manuscrit.

This thesis evaluated the effects of two types of training on nurses’ ability to safely and efficiently administer IV medications using a smart infusion pump. A high fidelity simulated nursing unit was created in which nurses recruited from the University Health Network programmed a series of infusions after receiving training. A training script modeled after the pump vendor’s training sessions was created and tested first on 24 nurses. The results were analyzed for deficiencies in safety and efficiency from a human factors and education perspective and a new training script was created and tested on a group of 23 nurses. No significant differences were found between training groups on measures related to safety, but significant differences were found in nurse efficiency and behaviour in some aspects of pump programming. This study sets a precedent for human factors evaluation being used in tandem with existing training practices and lays the groundwork for further exploration on this topic.

This thesis evaluated the effects of two types of training on nurses’ ability to safely and efficiently administer IV medications using a smart infusion pump. A high fidelity simulated nursing unit was created in which nurses recruited from the University Health Network programmed a series of infusions after receiving training. A training script modeled after the pump vendor’s training sessions was created and tested first on 24 nurses. The results were analyzed for deficiencies in safety and efficiency from a human factors and education perspective and a new training script was created and tested on a group of 23 nurses. No significant differences were found between training groups on measures related to safety, but significant differences were found in nurse efficiency and behaviour in some aspects of pump programming. This study sets a precedent for human factors evaluation being used in tandem with existing training practices and lays the groundwork for further exploration on this topic.

La maîtrise dimensionnelle des pièces composites représente un frein significatif à l'expansion large des matériaux composites. Ceci entraine une limitation de la complexité des pièces ainsi qu'une augmentation des assemblages de structure. Ces travaux s'intéressent en particulier aux déformations induites par le procédé d'infusion de résine. L'objectif étant d'améliorer la compréhension des interactions produit-procédé-ressources sur la géométrie finale de la pièce. Il a été mis en évidence, sur des pièces planes, un mécanisme de déformation spécifique au procédé d'infusion de résine résultant de l'interaction équipements d'infusion-pièce. Une analyse expérimentale a été mené afin d'identifier et de pondérer l'influence de paramètres procédé et ressources sur l'amplitude de gauchissement. A partir de ces résultats expérimentaux, un modèle de prédiction de l'amplitude de déformation a été mis en place et évaluer. Au vue du caractère spécifique du procédé d'infusion, des investigations ont été menés afin d'identifier la contribution de l'interaction équipements d'infusion-pièce sur des pièces en angle. Le renferment d'angle (ou " spring-in ") reste dominer par des contributions intrinsèques. Cependant, nos travaux ont mis en évidence une part non négligeable de l'angle mesuré résultant d'interactions avec les ressources. L'infusion de résine peut engendrer un transfert de contraintes significatif dans la pièce composite. Ces travaux permettent de les estimer en fonction de divers paramètres d'industrialisation.

Hepatocellular carcinoma (HCC) is the second most common cancer in Taiwan and transcatheter arterial chemoembolization (TACE) is now the mainstay of treatment for noncurative HCC. Due to increasing medical costs yearly and financial problem of the Bureau of National Health Insurance, it is important to reduce medical resource utilization including hospital stay and medical costs. The aim is to figure out the risk factors of extended hospital stay, and increased in-hospital medical costs in hepatocellular carcinoma patients receiving transcatheter arterial chemoembolization. The result of this study should be available for further improvement of medical care quality in the limited medical resource. From January 2008 to January 2010, 162 patients (121 male and 41 female) with histologically proven hepatocellular carcinoma underwent TACE only (131 pts) or TACE followed by catheter placement for hepatic artery infusion chemotherapy (HAIC) (31pts) at district teaching hospital. The extended hospital stay (EHS) and extended post-procedure stay (EPS) are defined as stay larger than their median values (11 & 7 days respectively). Clinical demographic, disease factors, tumor factors, procedure (TACE)-related factors and complications are used to identify the univariate factors related to EHS and EPS statistically. To find out predictors of EHS, EPS and increased in-hospital medical costs, multiple linear regression analyses are used. The risk factors for EPS are procedure-related, including complications and procedure methods ( TACE + HAIC related to TACE only) (R2=.367, p<.001), while those for EHS are complications, encephalopathy, procedure methods, Child-Pugh classification C (related to classification A) and age (R2=.490, p<.001). The predictors for increased in-hospital medical costs include procedure methods, AJCC stage IV, T4 stage, hepatoencephalopathy and complications (R2=0.615, p<.001). Taking total hospital stay into consideration, the most important risk factor related to increased medical cost is total hosptial stay itself. The most powerful risk factor for EPS, EHS is procedure-related complication. The different procedure methods also affect hospital stay and medical costs. In order to reduce medical resource utilization, we should avoid post-procedure complication and pay attention to cirrhotic degree as well as American Joint Committee of Cancer (AJCC) tumor stage system. The result of this study can provide some ideas to adjust medical expense polices for the Bureau of National Health Insurance and to control medical cost for the hospitals.

Die zytostatische Chemotherapie ist wesentlicher Bestandteil der palliativen Therapie von Patienten mit metastasiertem kolorektalen Karzinom. Gegenüber einer rein supportiven Behandlung verbessert eine auf 5-Fluorouracil (5-FU) basierende Chemotherapie die Lebensqualität und verlängert das Überleben der Patienten. 5- FU-Dauerinfusion moduliert mit Folinsäure ist die beste Grundlage für die Kombination mit Irinotecan oder Oxaliplatin. Randomisierte Studien zum Einsatz von Irinotecan zeigten signifikante Vorteile im Hinblick auf die Remissionsrate, das progressionsfreie Überleben und auch die mediane Überlebenszeit. Randomisierte Studien zum Einsatz von Oxaliplatin zeigten ebenfalls höhere Remissionsraten und ein verlängertes progressionsfreies Überleben ohne eine verlängerte Überlebenszeit nachweisen zu können. Heutzutage sollten alle Patienten mit einer Kombinationschemotherapie behandelt werden und im Verlauf ihrer Erkrankung, soweit möglich, alle zur Verfügung stehenden Medikamente erhalten. Nur dadurch können mediane Überlebenszeiten von über 20 Monaten erreicht werden. Der Einsatz oraler Fluoropyrimidine statt einer 5-FU-Dauerinfusion in Kombination mit Irinotecan und Oxaliplatin ist viel versprechend, jedoch Gegenstand laufender Studien. Monoklonale Antikörper gegen den EGF-Rezeptor bzw. gegen VEGF haben ebenfalls viel versprechende Ergebnisse gezeigt und werden wahrscheinlich die Behandlungsmöglichkeiten in der Zukunft wesentlich verbessern. / Systemic chemotherapy has a key role in the palliative treatment of patients with metastatic colorectal cancer. Compared to best supportive care, 5-fluorouracil (5-FU)-based therapy prolongs survival and improves quality of life. 5-FU continuous infusion modulated by Leukovorin (LV) is the optimal basis for a combination therapy with irinotecan or oxaliplatin. Randomized trials investigating the role of irinotecan in combination with 5-FU/LV relative to 5-FU/LV alone demonstrated a significant improvement in the response rate, progression free survival and overall survival. Randomized studies using oxaliplatin/ 5-FU/LV vs. FU/LV alone resulted in a higher response rate and longer progression-free survival while the overall survival was not significantly different. Today, all patients should receive combination treatment in first line and should be offered all active compounds during the course of their disease. Hereby, median survival times of more than 20 months are achievable. The use of oral fluoropyrimidines as a substitute of infusional 5-FU in combination with irinotecan or oxaliplatin is promising and subject of clinical trials. Monoclonal antibodies directed against the EGF-receptor or against VEGF have demonstrated interesting results and may be a treatment option in the future. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.